The risks to humans of exposure to neurotoxic organophosphorus pesticides has recently come to the public's attention. Workers in a factory in which leptophos (O-4-bromo-2,5-dichlorophenyl phenylphosphonate) was manufactured and packaged were poisoned; some developed paralysis. The overall objective of the total project is to determine the role of the skin as a potential portal of entry for these pesticides. This is determined by studying the ability of these compounds to cause delayed neurotoxicity following topical application, and by studying absorption, distribution, pharmacokinetic and metabolism of a topical single dose of 14C-labeled leptophos. The mechanism of delayed neurotoxicity will be investigated by studying the phosphorylation of mechanicokinetic proteins, and stability of lysosomal membranes, to determine if neuronal degeneration is initiated by the release of cellular hydrolases. In these studies, leptophos was proposed as the model compound, however, since this compound is now banned in the U.S. another neurotoxic insecticide, i.e. EPN and DEF will be included in some of the experiments.